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A tandem repeat in decay accelerating factor 1 is associated with severity of murine mercury-induced autoimmunity
Department of Surgery, University of California, San Diego, 9500 Gilman Drive, No. 0739, La Jolla, CA 92093-0739, USA.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
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2014 (engelsk)Inngår i: Autoimmune Diseases, ISSN 2090-0422, E-ISSN 2090-0430, Vol. 2014, nr 260613Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Decay accelerating factor (DAF), a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA). Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements.

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Hindawi Publishing Corporation, 2014. Vol. 2014, nr 260613
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-116712DOI: 10.1155/2014/260613PubMedID: 24818014Scopus ID: 2-s2.0-84900019378OAI: oai:DiVA.org:liu-116712DiVA, id: diva2:800103
Tilgjengelig fra: 2015-04-01 Laget: 2015-04-01 Sist oppdatert: 2018-01-16

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